Comparison of the effects of a new conjugated oral estrogen, estradiol-3β-glucoside, with oral micronized 17β-estradiol in postmenopausal women

The objective of this article is to evaluate the pharmacokinetics of serum estrone and estradiol levels in women who were taking either 17β-estradiol-3β-glucoside (E2-3β-glucoside) or 17β-estradiol (E2) daily and to examine the effects of E2-3β-glucoside and E2 on postmenopausal symptoms, gonadotropins, hepatic metabolism, and coagulation factors. Healthy postmenopausal women on estrogen who had undergone a hysterectomy were recruited. Subjects were randomly assigned to receive equivalent doses of either E2-3β-glucoside or micronized E2 for 28 days. Pharmacokinetic studies of estrone and estradiol were performed on days 1, 2, 28, and 29. Gonadotropin levels and Kupperman Index (KI) scores were determined at baseline and on treatment day 28. Mean serum estradiol and estrone concentrations in those taking E2-3β-glucoside were comparable with those taking E2. Mean baseline follicle stimulating hormone (FSH) levels were 84 ± 27 mIU/mL and 71 ± 24 mIU/mL in the E2-3β-glucoside and E2 groups, respectively, with significant decreases (P < 0.01) of 54 ± 21 mIU/mL and 38 ±18 mIU/mL, respectively, by treatment day 28. Baseline KI scores in the E2-3β-glucoside group were 10 ± 6 compared with 5 ± 4 on treatment day 28, which is equivalent to a 50% reduction in menopausal symptoms (P = 0.003). The change in KI scores in the E2 group was not statistically significant. Total serum estradiol and estrone levels in women taking E2-3β-glucoside are comparable with those in women taking E2. E2-3β-glucoside reduces serum gonadotropin levels to the premenopausal range and is effective at reducing postmenopausal symptoms. E2-3β-glucoside is a novel synthetic estrogen that is well tolerated and has promise as a hormone replacement therapy.